Patrick Almeida
University of Helsinki
Patrick Almeida is a pharmacy major and currently a PhD student at the Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Finland. He started his doctoral studies after obtaining his Master’s Degree in Pharmaceutical Sciences from the Faculty of Pharmacy, University of Coimbra, Portugal, in July 2012. During his PhD studies, he has been mainly focused on developing porous silicon-based multifunctional nanocomposites for cancer targeting, drug delivery and theranostic applications, and has co-authored twelve scientific publications. Recently, Patrick Almeida has been working as a visiting PhD student at the German Cancer Research Center, in Heidelberg, Germany.
Introduction
Over the past few decades, breakthroughs in nanotechnology have paved the way for a new era of cancer theranostics.[1]
Porous silicon (PSi) nanoparticles have demonstrated tremendous potential for drug delivery applications, owing to their physicochemical and biological properties, with particular emphasis in cancer nanomedicine.[2] However, its limited cellular internalization and the incapacity for escaping endosomes still stand as deadlocks defying the implementation of these nanocarriers as anticancer drug delivery systems.
An interesting approach for improving the cellular internalization and intracellular trafficking of nanomedicines involves the design of multivalent cationic non-viral vectors.[3] For that purpose, cationic polymers have been used to complex negatively charged encapsulates, generating supramolecular nanostructures known as polyplexes.[4]
Objective
Herein, we envisioned to fabricate a multifunctional nano-in-nanocomplex platform encapsulating both sorafenib (SFB)-loaded PSi and gold (Au) nanoparticles into a polymeric nanocomplex (CPP) (Figure 1A). This novel approach aims to enhance the interaction of the PSi nanocarriers with cancer cells and induce their endosomal escape, ultimately improving the cytoplasmatic delivery and, consequently, the chemotherapeutic efficacy of the loaded anticancer agents.
Materials and Methods
The nanocomposites were physicochemically characterized and evaluated in vitro for cyto- and hemocompatibility, cellular association and internalization, endosomolytic properties, cytoplasmatic drug delivery and chemotherapeutic effect.
Results and Discussion
The nanocomposites were successfully produced and exhibited adequate physicochemical properties (Figure 1B, 1C), as well as superior in vitro cyto- and hemocompatibilities. The encapsulation of PSi nanoparticles in the nanocomplexes significantly enhanced their cellular internalization and enabled their endosomal escape (Figure 2), resulting in the efficient cytoplasmic delivery of these nanosystems. Sorafenib-loaded nanocomposites showed a potent in vitro anti-proliferative effect on MDA-MB-231 breast cancer cells (Figure 3).
Conclusion
The multifunctional nanocomposites showed great promise for the cytoplasmatic delivery of chemotherapeutics, as well as for the further development as nanoplatforms for cancer theranostic applications.
References
[1] S. S. Kelkar, T. M. Reineke, Bioconjug Chem 2011, 22, 1879-1903.
[2] H. A. Santos, E. Mäkila, A. J. Airaksinen, L. M. Bimbo, J. Hirvonen, Nanomedicine (Lond) 2014, 9, 535-554
[3] E. Junquera, E. Aicart, Adv Colloid Interface Sci 2016, 233, 161-175.
[4] U. Lachelt, E. Wagner, Chem Rev 2015, 115, 11043-11078.
Targeted drug delivery and nanocarriers , Nanomedicine for cancer diagnosis & therapy
